OVERALL ? PROJECT SUMMARY/ABSTRACT This application seeks renewed CCSG funding for the University of Virginia (UVA) Cancer Center, a matrix cancer center that brings together 132 Members from 26 Departments in the Schools of Medicine, Nursing, and Engineering, and in the College of Arts and Sciences. The UVA Cancer Center receives $25.96M from NCI, $32.65M from other peer-reviewed sources, and $4.36M from non-peer-reviewed sources, for a total of $62.97M in overall funding. Through faculty recruitment and robust infrastructure development, the UVA Cancer Center has continued to build on its exceptional basic science foundations and has greatly enhanced its ability to accelerate clinical and translational cancer focused research. Since the last renewal, over 50 new faculty have been recruited, including twenty-four clinical investigators and/or physician-scientists and twenty- six laboratory scientists, bioengineers, population, and computational biologists. The Cancer Center has five Programs: Chemical and Structural Biology (CSB), Molecular Genetics and Epigenetics (GEN), Cancer Cell Signaling (SIG), Immunology/Immunotherapy (IMM), and Women's Oncology (WON). This application requests support for seven Shared Resources: Advanced Microscopy Facility (AMF), Animal Models of Disease Core (AMDC), Biomolecular Analysis Facility (BAF), Bioinformatics Core (BIC), Biorepository and Tissue Research Facility (BTRF), Biostatistics Shared Resource (BSR), and Flow Cytometry Core (FCC). In addition, we request support for Clinical Protocol and Data Management (CPDM) infrastructure and a Protocol Review and Monitoring System (PRMS). A completely transformed infrastructure for translational and clinical research facilitates investigations using human tissues and the implementation of clinical trials. Substantial new initiatives have been launched to reach underserved populations in Appalachia. This renewal application describes continued outstanding basic cancer research, enhanced cancer focus, and greatly strengthened clinical research leadership and infrastructure.